Haploidentical donor hematopoietic stem cell transplantation for blastic plasmacytoid dendritic cell neoplasm treatment
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摘要: 目的探讨异基因造血干细胞移植治疗母细胞性浆细胞样树突细胞肿瘤(BPDCN)的疗效及患者生存情况。方法回顾性分析该中心13例诊断为BPDCN的患者，均接受清髓预处理方案(MAC)的单倍型供者造血干细胞移植(HID-HSCT)。结果所有患者均以髓外病变为初发表现(皮肤病变11例，乳房1例，淋巴结1例)，均涉及骨髓，其中2例合并中枢神经系统侵犯。在进行HID-HSCT前，所有患者均达到缓解状态(9例CR1，4例CR2)，其中4例微小残留白血病阳性。所有患者干细胞均顺利植入，其中1例患者出现移植物功能不良，3例患者出现Ⅱ~Ⅳ级急性移植物抗宿主病，5例患者出现慢性移植物抗宿主病(4例轻度, 1例中度)。生存患者的中位随访时间为34(5~64)个月, 无病生存率为(76.9±12.6)%。3例患者死亡(1例急性移植物抗宿主病，1例复发，1例移植后血栓性微血管病/移植物抗宿主病)。结论采用MAC的HID-HSCT治疗BPDCN患者安全有效。
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关键词:
- 单倍型供者 /
- 造血干细胞移植 /
- 清髓预处理方案 /
- 母细胞性浆细胞样树突细胞肿瘤
Abstract: ObjectiveAllogeneic hematopoietic stem cell transplantation may be the only way to cure blastic plasmacytoid dendritic cell neoplasm(BPDCN).MethodsIt retrospectively analyzed 13 patients with BPDCN who received haploidentical donor hematopoietic stem cell transplantation(HID-HSCT) with myeloablative conditioning regimens(MAC).ResultsAll patients had extramedullary lesions as the initial manifestation(11 cases of skin lesions, 1 case of breast, 1 case of lymph node). All of them had bone marrow invasion, two of which had central nervous system invasion. Before HID-HSCT, all patients got complete remission(9 cases of CR1, 4 cases of CR2), 4 of them were positive for minimal residual leukemia. Stem cells were successfully implanted in all patients, 1 patient with graft dysfunction, 3 patients with grade Ⅱ-Ⅳacute graft-versus-host disease, and 5 patients with chronic graft-versus-host disease(4 mild, 1 moderate). The median follow-up time of survived patients was 34(5-64) months, the disease-free survival was (76.9±12.6)%. Three patients died(1 case of aGVHD, 1 case of relapse, 1 case of TMA/GVHD).ConclusionHID-HSCT with MAC is safe and effective for BPDCN treatment. -
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表 1 患者移植前疾病特征
患者 性别/年龄/岁 初发病变部位 累及骨髓或中枢 细胞遗传学 基因突变 移植前化疗方案 诊断至移植的时间/月 移植前疾病状态 1 男/43 皮肤损害/淋巴结肿大 是/是 正常 TP53+/SH2B+/PAX5+ NHL样(n=2)
AML样(n=1)6 CR1/MRD- 2 女/39 乳腺肿块 是/否 缺失 阴性 NHL样(n=6)
AML样(n=1)8 CR2/MRD- 3 女/49 皮肤损害 是/否 缺失 阴性 NHL样(n=3)
ALL样(n=3)
AML样(n=2)19 CD2/MRD- 4 女/6 淋巴结肿大 是/否 复杂核型 NRAS+/BCL2+ NHL样(n=2)
ALL样(n=1)6 CR1/MRD 0.09% 5 男/37 皮肤损害/淋巴结肿大 是/否 正常 阴性 NHL样(n=1)
ALL样(n=2)4 CR1/MRD- 6 男/8 皮肤损害 是/否 缺失 阴性 ALL样(n=2)
NHL样(n=6)
HID-HSCT(n=1)
CD123+
CAR-T(n=2)30 CR2/MRD- 7 男/15 皮肤损害 是/否 正常 CDKN1B+/RELN NHL样(n=2)
ALL样(n=2)12 CR1/MRD 0.03% 8 男/37 皮肤损害 是/否 46，XY，t(9：16)
(q22；q24)[10]阴性 ALL样(n=1)
AML样(n=2)9 CR1/MRD 0.01% 9 男/10 皮肤损害 是/是 46，XY，t(2；4)
(p23；p16)[20]CEBPA+ ALL样(n=6)
AML样(n=2)32 CR2/MRD- 10 男/13 皮肤损害 是/否 复杂 阴性 AML样(n=2) 2 CR1/MRD 0.72% 11 女/12 皮肤损害 是/否 43~45，XX，-C，del(6)(q21)，
del(7)(q32)+mar，
inc[cp9]/46，XX[11]阴性 NHL样(n=2) 4 CR1/MRD- 12 男/70 皮肤损害 是/否 缺失 TET2+/BRAF+/CCND1+/RUNX1+ AML样(n=2) 8 CR1/MRD- 13 男/36 皮肤损害 是/否 46，XY[30]，另见一个核型：46，XY，t(9；13)(q22；q34) ATM+ NHL样(n=3)
ALL样(n=1)12 CR2/MRD- 
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表 2 供者及移植特征
患者 供受者关系 血型 预处理方案 MNC/(108·kg-1) CD34+/(106·kg-1) WBC/PLT植入时间(移植后天数)/d aGVHD/时间、部位、级别 cGVHD 生存状态/死亡原因/随访时间/月 1 儿子供父亲 A→A Dec/Arac/Bu/Cy 9.52 4.50 23/未植活 90 d，肝、肠，Ⅳ级 无 死亡/aGVHD
(DLI相关)/42 哥哥供弟弟 O→B IDA/Ara-c/Bu/Cy 12.87 5.08 10/13 26 d，皮肤，Ⅰ级 轻度 无病生存/64 3 儿子供母亲 B→B IDA/Ara-c/TBI/Cy 7.49 5.02 11/10 15 d，皮肤、肠道，Ⅱ级 轻度 无病生存/58 4 父亲供女儿 B→A IDA/Ara-c/Bu/Cy 7.99 3.98 15/13 无 中度 无病生存/47 5 姐姐供弟弟 A→B Ara-c/Bu/Flu 9.94 5.00 12/28 无 无 无病生存/40 6 父亲供儿子 O→O Ara-c/Bu/Flu 10.05 5.00 11/7 无 无 死亡(复发)/5 7 父亲供儿子 B→B IDA/Ara-c/Bu/Flu 7.89 4.90 11/10 无 无 无病生存/36 8 父亲供儿子 O→A IDA/Ara-c/TBI/Cy 3.98 6.01 14/13 无 轻度 无病生存/34 9 父亲供儿子 A→A IDA/Ara-c/TBI/Cy 13.60 4.09 15/19 无 轻度 无病生存/31 10 父亲供儿子 O→B Dec/Ara-c /TBI/Cy 5.49 4.56 12/12 4个月，皮肤、肠道，Ⅳ级 无 死亡(GVHD/TMA)/6 11 父亲供女儿 O→O IDA/Ara-c/TBI/Cy 8.01 4.50 12/10 无 无 无病生存/9 12 女儿供父亲 O→A TT/BU/FLU 8.04 5.00 14/17 无 无 无病生存/6 13 父亲供儿子 O→O Ara-c/TBI/Cy 14.12 7.41 14/18 无 无 无病生存/5
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